The following disorders are unique genetic neurological disorders that result in varied clinical presentations and outcomes for patients.              Neurofibromatosis divided into type one (NF1) and type 2 (NF2) are autosomal dominant neurocutaneous disorders that results in altered genes that causes dysregulation of tumor suppression (Defendi, 2022).  NF1 is more common and occurs in one out of every 3,500 births (Germanwala, n.d.).  NF1, there is a deletion of the NF1 gene that produces neurofibromin 1 that activates the protein ras-GTPas which is involved with cellular signal transduction (Defendi, 2022).  Without the NF1 gene there is an overactive ras-GTPas resulting in the activation of other proteins, in turn activating genes for cell growth and differentiation leading to benign or malignant tumors (Defendi, 2022).  Common benign tumors include cutaneous neurofibromas, plexiform neurofibromas and optic nerve gliomas (Defendi, 2022).  Patients with NF1 present with a family history of the disorder, six or more of the café-au-lait spots on the skin, freckling in the underarms and groin, presence neurofibromas (about pea-sized) on or just under skin, plexiform neurofibromas, Lisch nodules, skeletal abnormalities and have the potential for tumors on the optic nerve (Germanwala, n.d.).  Additionally, these patients may present with macrocephaly, short stature, are at risk for seizures, learning disabilities, speech issues and hyperactivity (Germanwala, n.d.).  Cri-du-chat syndrome is a chromosomal disorder, also known as 5p minus syndrome where there is a deletion of the variable size on the short arm of chromosome 5 (Mainardi, 2006).  Since this disorder is a syndrome, there are several clinical features that are common in the presentation of this disorder including microcephaly, large nasal bridge, hypertelorism, epicanthal folds, downward slanting palpebral fissures, down-turned corners of the mouth, low-set ears, micrognathia, abnormal dermatoglyphics and the hallmark high-pitched cry (Mainardi, 2006).  The cry is a result of structural abnormalities of the larynx caused by laryngeal hypoplasia and central nervous system (Lal, 2021).  The central nervous system deficit is noted in the “…clivus region of the cranial base with the laryngeal region from which the characteristic cry derived” (Lal, 2021).  Neurologically, these patients have developmental and psychomotor delay, with varied levels of abilities.  Patients also present with hypotonia which progresses to hypertonia with age.  On magnetic nuclear resonance imaging, brainstem atrophy has been noted including the pons, cerebellum, median cerebellar peduncles and cerebellar white matter” (Mainardi, 2006). Tay-Sachs Disease also known as GM2 gangliosidosis, is a fatal autosomal recessive disorder caused by the HexA gene found on chromosome 15 (McCance & Huether, 2014).   The deficiency in the lysosomal enzyme hexosaminidase A (HexA) results in decreased degradation in GM2 gangliosi.

1. The following disorders are unique genetic neurological
disorders that result in varied clinical presentations and
outcomes for patients.
Neurofibromatosis divided into type one (NF1) and type
2 (NF2) are autosomal dominant neurocutaneous disorders that
results in altered genes that causes dysregulation of tumor
suppression (Defendi, 2022). NF1 is more common and occurs
in one out of every 3,500 births (Germanwala, n.d.). NF1, there
is a deletion of the NF1 gene that produces neurofibromin 1 that
activates the protein ras-GTPas which is involved with cellular
signal transduction (Defendi, 2022). Without the NF1 gene
there is an overactive ras-GTPas resulting in the activation of
other proteins, in turn activating genes for cell growth and
differentiation leading to benign or malignant tumors (Defendi,
2022). Common benign tumors include cutaneous
neurofibromas, plexiform neurofibromas and optic nerve
gliomas (Defendi, 2022). Patients with NF1 present with a
family history of the disorder, six or more of the café-au-lait
spots on the skin, freckling in the underarms and groin,
presence neurofibromas (about pea-sized) on or just under skin,
plexiform neurofibromas, Lisch nodules, skeletal abnormalities
and have the potential for tumors on the optic nerve
(Germanwala, n.d.). Additionally, these patients may present
with macrocephaly, short stature, are at risk for seizures,
learning disabilities, speech issues and hyperactivity
(Germanwala, n.d.).
Cri-du-chat syndrome is a chromosomal disorder, also known as
5p minus syndrome where there is a deletion of the variable size
on the short arm of chromosome 5 (Mainardi, 2006). Since this
disorder is a syndrome, there are several clinical features that
are common in the presentation of this disorder including
microcephaly, large nasal bridge, hypertelorism, epicanthal
folds, downward slanting palpebral fissures, down-turned
corners of the mouth, low-set ears, micrognathia, abnormal

2. dermatoglyphics and the hallmark high-pitched cry (Mainardi,
2006). The cry is a result of structural abnormalities of the
larynx caused by laryngeal hypoplasia and central nervous
system (Lal, 2021). The central nervous system deficit is noted
in the “…clivus region of the cranial base with the laryngeal
region from which the characteristic cry derived” (Lal, 2021).
Neurologically, these patients have developmental and
psychomotor delay, with varied levels of abilities. Patients also
present with hypotonia which progresses to hypertonia with
age. On magnetic nuclear resonance imaging, brainstem
atrophy has been noted including the pons, cerebellum, median
cerebellar peduncles and cerebellar white matter” (Mainardi,
2006).
Tay-Sachs Disease also known as GM2 gangliosidosis, is a fatal
autosomal recessive disorder caused by the HexA gene found on
chromosome 15 (McCance & Huether, 2014). The deficiency
in the lysosomal enzyme hexosaminidase A (HexA) results in
decreased degradation in GM2 gangliosides or fatty acids within
nerve cell lysosomes (McCance & Huether, 2014). This build
up results in toxic levels of GM2 gangliosides in the neurons
throughout the body resulting in misshaped neurons and
microglial cells (McCance & Huether, 2014). Leading to cystic
degeneration of the cerebral white matter, atrophy of the
cerebellar hemispheres and changes in the spinal cord (McCance
& Huether, 2014). This disorder in patients presents in infants
between three to six months of ages with noted loss of
milestones with an overactive startle response (McCance &
Huether, 2014). Other signs and symptoms include hypotonia,
hyporeflexia, muscle rigidity, blindness and increased head
circumference (McCance & Huether, 2014).
Early onset Parkinson’s Disease or Juvenile parkinsonism (JP)
is parkinsonian signs and symptoms prior to 21 years.
“Levodopa-responsive juvenile parkinsonism that is consistent
with diagnostic criteria for Parkinson's disease is most often
caused by mutations in the PARK-Parkin, PARK-PINK1, or
PARK-DJ1 genes (Niemann & Jankovic, 2019). The overall

3. pathophysiology is not understood, but it is clear in the body of
research that there is a clear relationship between these genes
that impact mitochondrial function and oxidative stress response
(Cookson, 2012). Most JP patients do not meet the diagnostic
criteria for Parkinson’s Disease. Instead, they present with
“…disproportionate severity of another movement disorder
(e.g., dystonia, ataxia, spasticity), early cognitive decline,
severe behavioral disturbance, or relevant medical history such
as exposure to dopamine receptor blocking agents (DRBA),
head trauma, brain tumor, and other secondary causes”
(Niemann & Jankovic, 2019).
Overall, these disorders reflect the complexities of our genetics
and our nervous system. It was evident throughout my research
that couples with any knowledge of familial history of any
genetic disorders should consider genetic counseling prior to
having children.
Cookson M. R. (2012). Parkinsonism due to mutations in
PINK1, parkin, and DJ-1 and oxidative stress and mitochondrial
pathways. Cold Spring Harbor perspectives in medicine, 2(9),
a009415. https://doi.org/10.1101/cshperspect.a009415
Defendi, G. L., MD. (2022, October 10). Genetics of
Neurofibromatosis Type 1 and Type 2: Overview, NF Genes,
Genetic Testing.
https://emedicine.medscape.com/article/950151- overview
Germanwala, A. (Ed.). (n.d.). Neurofibromatosis – Symptoms,
Diagnosis and Treatments. American Association of
Neurological Surgeons.
https://www.aans.org/en/Patients/Neurosurgical-Conditions-
and- Treatments/Neurofibromatosis
Lal, M. K., MD. (2021, March 7). Cri-du-chat Syndrome:
Practice Essentials, Pathophysiology, Epidemiology.
https://emedicine.medscape.com/article/942897-overview
Mainardi, C. P. (2006, September 5). Cri du Chat syndrome -
Orphanet Journal of Rare Diseases. BioMed Central.
https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-1-33
Niemann, N., & Jankovic, J. (2019). Juvenile parkinsonism:

4. Differential diagnosis, genetics, and treatment. Parkinsonism
&Amp; Related Disorders, 67, 74–89.
https://doi.org/10.1016/j.parkreldis.2019.06.025
McCance, K.L. & Huether, S.E. (Eds.). (2014).
Pathophysiology: The biologic basis for disease in adults and
children. (7th. ed.). Elsevier Mosby.
https://online.vitalsource.com/books/9780323088541
· Discuss the pathophysiology of cerebrovascular accidents
(CVAs)—thrombotic, embolic, hemorrhagic, and lacunar—their
incidence and prevalence, clinical manifestations, evaluation,
and treatment. P. 598
Pathophysiology of cerebrovascular accidents (CVAs) is any
abnormality or blockage of blood flow to the brain leading to a
stroke. There are different types of strokes along with different
areas where strokes can take place in the brain leading to
different neurological deficits in the patient (McCance &
Huether, 2014).
A thrombotic stroke is where thrombi have formed within the
arteries or intracranial vessels supplying the brain. An embolic
stroke is when an embolus has formed outside the brain and
travels to the brain via the bloodstream. Thrombotic and
embolic strokes, also known as ischemic strokes are the most
common, accounting for 87% of the strokes that occur
(McCance & Huether, 2014).
The clinical manifestations of a thrombotic or embolic stroke
are contralateral hemiparesis or hemiplegia, expressive aphasia,
and dysphagia, hemianopia and quardranopsia. A simple
screening tool for clinical manifestations of a stroke is BE-
FAST. Balance, Eyes, Face, Arm, Speech, Time.
“Time is brain” is the classic saying when dealing with the

5. evaluation and treatment of thrombotic and embolic stroke.
Restoring brain perfusion is the number one priority followed
by preventing recurrent strokes from happening. Treatment
consists of recognizing the signs and symptoms of a stroke early
on. Once diagnostic imaging such as a Cat scan of the head, has
taken place and the type of stroke has been determined, the
patient will either receive tissue plasminogen activator (TPA) if
not contraindicated, to break down the clot or be taken to the
operating room for surgical clipping or craniotomy if the stroke
is hemorrhagic.
Hemorrhagic stroke is when a blood vessel within the brain
spontaneously begins to bleed. This is the third most common
stroke (McCance & Huether, 2014) Priority treatment for
hemorrhagic strokes is to stop the bleeding, prevent rebleeding
and hematoma enlargement, control intracranial pressure,
control vasospasms, Seizure prophylaxis is implemented due to
damage in the brain as a result of the stroke.
Lacunar strokes are also a type of ischemic stroke where the
infarct is very small and blockages are found deep within the
brain structures such as the thalamus or basal ganglia. Lacunar
strokes account for 15%-25% of ischemic strokes.
Aldriweesh, M. A., Alluhidan, W. A., Al Bdah, B. A., Alhasson,
M. A., Alsaif, S. A., Alajlani, A. A., Almutairi, F. M., Alskaini,
M. A., Alotaibi, N., & Al Khathaami, A. M. (2021). Prevalence
and Clinical Characteristics of Lacunar Stroke: A Hospital-
Based Study.
Brain sciences,
11(11), 1466.
https://doi.org/10.3390/brainsci11111466
Links to an external site.
McCance, K.L. & Huether, S.E. (Eds.). (2014).
Pathophysiology: The biologic basis for disease
in adults and children. (7th. ed.). Elsevie